A canine model of acute hypercapnic respiratory failure has been developed. The left hemidiaphragm is made to contract using transvenous stimulation of the left phrenic nerve. Variable resistances are added to the inspiratory limb of the breathing circuit to provide progressively severe work loads. Diaphragm muscle tisuse metabolites (ATP, creatine phosphate, creatine, lactate, glycogen) are analyzed after one hour, at which time the degrees of hypoxemia, hypercapnia, acidosis depend both on the strength and endurance of the working hemidiaphragm and the severity of the ventilatory load. Initial results in this model have shown that the working left hemidiaphragm can be depleted of ATP and creatine phosphate, especially the latter, when the whole animal become acidemic and hypoxic. Under these conditions, creatine and lactate concentrations in the working hemidiaphragm increase. In contrast, there is no significant change in any of these metabolites in the resting right hemidiaphragm. Subsequent studies will analyze the effects of spontaneous breathing instead of electrophrenic pacing, and will attempt to separate the effects of acidosis from those of hypoxia. In addition, it is planned to utilize an open-chest preparation to measure diaphragm tension directly, so as to compare metabolic events in the muscle with its contractility profile.